Dietary High Dose of Iron Aggravates the Intestinal Injury but Promotes Intestinal Regeneration by Regulating Intestinal Stem Cells Activity in Adult Mice With Dextran Sodium Sulfate-Induced Colitis

Yitong Zhang; Lanmei Yin; Xianglin Zeng; Jun Li; Yuebang Yin; Qiye Wang; Jianzhong Li; Huansheng Yang

doi:10.3389/fvets.2022.870303

Dietary High Dose of Iron Aggravates the Intestinal Injury but Promotes Intestinal Regeneration by Regulating Intestinal Stem Cells Activity in Adult Mice With Dextran Sodium Sulfate-Induced Colitis

Front Vet Sci. 2022 Jun 15:9:870303. doi: 10.3389/fvets.2022.870303. eCollection 2022.

Authors

Yitong Zhang¹, Lanmei Yin^{1

2

3}, Xianglin Zeng¹, Jun Li^{1

4}, Yuebang Yin², Qiye Wang^{1

3}, Jianzhong Li¹, Huansheng Yang^{1

2

4}

Affiliations

¹ Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, China.
² Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.
³ National Center of Technology Innovation for Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Beijing, China.
⁴ State Key Laboratory of Food Safety Technology for Meat Products, Yinxiang Group, Fujian Aonong BiologicaI Science and Technology Group Co., Ltd., Key Laboratory of Swine Nutrition and Feed Science of Fujian Province, Aonong Group, Zhangzhou, China.

Abstract

The effects of excessive dietary iron intake on the body have been an important topic. The purpose of this study was to investigate the effects of high-dose iron on intestinal damage and regeneration in dextran sodium sulfate (DSS)-induced colitis model mice. A total of 72 8-week-old adult C57BL/6 mice were randomly divided into two dietary treatment groups: the basal diet supplemented with 45 (control) and 450 mg/kg iron (high-iron) from ferrous sulfate. The mice were fed different diets for 2 weeks, and then 2.5% DSS was orally administered to all mice for 7 days. Samples of different tissues were collected on days 0, 3, and 7 post administration (DPA). High-iron treatment significantly decreased the relative weight of the large intestine at 7 DPA but not at 0 DPA or 3 DPA. High dietary iron increased the jejunal villus width at 0 DPA, decreased the villus width and the crypt depth of the jejunum at 3 DPA, and decreased the number of colonic crypts at 7 DPA. Meanwhile, high dietary iron decreased the number of goblet cells in the jejunal villi and the Paneth cells in the jejunal crypts at 0 DPA, increased the number of goblet cells per crypt of the colon at 3 DPA, and the number of Paneth cells in the jejunal crypts, the goblet cells in the colon, the Ki67-positive proliferating cells in the colon, and the Sex-determining region Y-box transcription factor 9⁺ (SOX9) cells in the jejunum crypts and colon at 7 DPA. The organoid formation rate was increased by high-iron treatments at 3 DPA and 7 DPA. High dietary iron treatment decreased the mRNA level of jejunal jagged canonical Notch ligand 2 (Jag-2) at 0 DPA and bone morphogenetic protein 4 (Bmp4) and neural precursor cell-expressed developmentally downregulated 8 (Nedd8) in the jejunum and colon at 7 DPA, whereas it increased the mRNA expression of the serum/glucocorticoid-regulated kinase 1 (Sgk1) in the colon at 3 DPA. The results suggested that a high dose of iron aggravated intestinal injury but promoted intestinal repair by regulating intestinal epithelial cell renewal and intestinal stem cell activity in adult mice with colitis.

Keywords: adult mice; dextran sodium sulfate-induced colitis; high iron; intestinal injury; intestinal repair.